The goal of the Pilot/Demonstration Progam is to conduct early phase research studies what will advance our knowledge about immune mediated disorders after allogeneic hematopoietic cell transplantation (HCT). We propose three pilot studies focused on clinical/translational research. Additional pilot studies may be funded or may replace these studies, depending on evolving knowledge in the field. Pilot 1 focuses on bronchiolitis obliterans syndrome (BOS) and proposes a small (N=40) clinical trial testing a treatment approach targeting the innate and adaptive immune system using a combination of fluticasone, azithromycin and montelukast. All three agents are relatively nontoxic FDA-approved medications with preliminary data suggesting benefit in both the lung transplant and allogeneic HCT BOS settings. Biomarker studies from bronchoalveolar fluid and blood will complement clinical assessment of response using serial pulmonary function tests. Two other pilot studies currently planned for the later half of the funding period focus on the pathophysiology and treatment of late acute graft versus host disease (GVHD). One is a clinical trial potentially testing alefacept, an agent targeted to memory T cells. The other is a laboratory study to evaluate whether effector or memory T cell populations specific for recipient alloantigens are associated with late acute and classic chronic GVHD. Selection of pilot projects and management of the Pilot/Demonstration Program is the responsibility of the Rare Diseases Clinical Research Consortium (RDCRC) PI with input from other members of Consortium. Criteria for pilot project selection emphasize scientific potential and integration/synergy with other RDCRC initiatives. Mechanisms for quality assurance, data management, Data Safety Monitoring Board oversight and interactions with the entire Consortium will mirror the procedures established for the Projects. We will work closely with NIH program officers to ensure that the Pilot Program is fulfilling the funding intention.